BJ-3105, a 6-Alkoxypyridin-3-ol Analog, Impairs T Cell Differentiation and Prevents Experimental Autoimmune Encephalomyelitis Disease Progressionopen access
- Authors
- Timilshina, Maheshwor; Kang, Youra; Dahal, Ishmit; You, Zhiwei; Nam, Tae-Gyu; Kim, Keuk-Jun; Jeong, Byeong-Seon; Chang, Jae-Hoon
- Issue Date
- Jan-2017
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- MULTIPLE-SCLEROSIS; ENCEPHALITOGENIC ANTIGENS; IMMUNE DEVIATION; TH17 CELLS; IN-VIVO; GM-CSF; CYTOKINES; IL-17; PATHOGENESIS; INDUCTION
- Citation
- PLOS ONE, v.12, no.1, pp.1 - 18
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 12
- Number
- 1
- Start Page
- 1
- End Page
- 18
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/10532
- DOI
- 10.1371/journal.pone.0168942
- ISSN
- 1932-6203
- Abstract
- CD4(+) T cells are essential in inflammation and autoimmune diseases. Interferon-gamma (IFN-gamma) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-gamma and IL-17 production from polyclonal CD4(+) T cells and ovalbumin (OVA)-specific CD4(+) T cells which were activated by T cell receptor (TCR) engagement. BJ-3105 ameliorated the experimental autoimmune encephalomyelitis (EAE) model by reducing Th1 and Th17 generation. Notably, Th cell differentiation was significantly suppressed by BJ-3105 treatment without inhibiting in vitro proliferation of T cells or inducing programmed cell death. Mechanistically, BJ-3105 inhibited the phosphorylation of JAK and its downstream signal transducer and activator of transcription (STAT) that is critical for Th differentiation. These results demonstrated that BJ-3105 inhibits the phosphorylation of STAT in response to cytokine signals and subsequently suppressed the differentiation of Th cell responses.
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